Topical Janus kinase inhibitors for the treatment of pediatric alopecia areata

To the Editor: Alopecia areata (AA) is a common and often recalcitrant condition with potentially devastating emotional and psychosocial effects. There are several case reports and series regarding the use of oral Janus kinase (JAK) inhibitors for treatment of AA and, more recently, 2 open-label clinical trials.1Craiglow B.G. King B.A. Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis.J Invest Dermatol. 2014; 134: 2988-2990Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 2Kennedy Crispin M. Ko J.M. Craiglow B.G. et al.Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.JCI Insight. 2016; 1: e89776Crossref PubMed Scopus (213) Google Scholar, 3Mackay-Wiggan J. Jabbari A. Nguyen N. et al.Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata.JCI Insight. 2016; 1: e89790Crossref PubMed Scopus (176) Google Scholar Oral JAK inhibitors have been associated with adverse effects including serious infections in up to 2%-6% of patients.4Kavanaugh AF, Geier J, Bingham C, et al. Real world results from a post-approval safety surveillance of tofacitinib (Xeljanz): over 3 year results from an ongoing US-based rheumatoid arthritis registry. Presented at: American College of Rheumatology Annual Meeting; Nov. 11-16, 2016; Washington, DC.Google Scholar Topical formulations might offer decreased risk compared with systemic therapy. To date, there has been 1 report of a teenage girl with alopecia universalis who experienced significant hair regrowth with use of ruxolitinib 0.6% cream.5Craiglow B.G. Tavares D. King B.A. Topical ruxolitinib for the treatment of alopecia universalis.JAMA Dermatol. 2016; 152: 490-491Crossref PubMed Scopus (80) Google Scholar We report 6 pediatric AA patients treated with topical JAK inhibitors. Our findings are summarized in Table I. Topical preparations included tofacitinib and ruxolitinib creams in 1% and 2% formulations prepared by a compounding pharmacy. All but one patient had previously failed multiple conventional treatments. Before initiation of therapy, baseline laboratory assessment, including complete blood count; liver enzymes; blood urea nitrogen; creatinine; and screening for tuberculosis, human immunodeficiency virus, and hepatitis viruses B and C, was performed for 4 of 6 patients. The remaining 2 patients (1 and 3) did not undergo baseline laboratory screening because they applied the cream to a limited body surface area (eyebrows), and the potential for systemic absorption was thought to be low. Follow-up laboratory monitoring included at a minimum complete blood count, alanine aminotransferase, blood urea nitrogen, and creatinine.Table IPatient characteristics, treatments, and responsePatient no.SexAge, yPMHDxAge at onsetTime since patient had substantial scalp hairPreviously failed treatmentsTopical JAK inhibitor therapyResponse to therapyLaboratory abnormalities1M13Hashimoto thyroiditis, euthyroid on levothyroxineAU2 y2 yTopical and intralesional corticosteroidsTofacitinib 2% in liposomal base to eyebrow regions BID × ∼3 mos∼20% regrowth of medial eyebrowsNot monitored2M4NoneAU3 y18 mTopical and intramuscular corticosteroids, SADBERuxolitinib 2% in liposomal base to eyebrow regions BID then tofacitinib 1% in liposomal base BID × 3 mosNoneNone3F17NoneAU3 y3 yTopical and intralesional corticosteroidsRuxolitinib 1% in liposomal base to eyebrow regions & upper eyelids BID × 18 mos∼75% regrowth of upper lashes; no regrowth of eyebrowsNot monitored4F15Mild anemia, resolved with iron supplement with no regrowth of hairAA14 yN/AOral and intralesional corticosteroids, anthralinTofacitinib 2% in VersaBase cream to areas of scalp alopecia QOD × 3 mos, then tofacitinib 2% in liposomal base QOD × 9 mosNo response to tofacitinib in VersaBase cream; 95% regrowth with liposomal base formulationWBC 3.3 (ref: 4.5-11 K/mm3) after 10 mos of treatment; increased to 5.4 K/mm3 1 mo later5F3Hemolytic disease of the newbornAT16 mos6 mosNoneTofacitinib 2% in liposomal base to affected areas of scalp BID∼30% regrowth after 1 mo; 80% regrowth after 1 yBaseline AST/ALT 43/35 IU/L (ref: 5-41/6-40 IU/L); max AST/ALT 51/42 IU/L; most recent AST/ALT 43/25 IU/L6F5NoneAT18 mos3 yTopical and oral corticosteroids, tacrolimus, minoxidil, methotrexateTofacitinib 2% in liposomal base to affected areas of scalp BID × 3 mosNo responseNoneAA, Alopecia areata; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AT, alopecia totalis; AU, alopecia universalis; BID, twice daily; Dx, diagnosis; F, female; JAK, Janus kinase; M, male; N/A, not applicable; PMH, past medical history; QOD, every other day; SADBE, squaric acid dibutylester; WBC, white blood cell count. Open table in a new tab AA, Alopecia areata; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AT, alopecia totalis; AU, alopecia universalis; BID, twice daily; Dx, diagnosis; F, female; JAK, Janus kinase; M, male; N/A, not applicable; PMH, past medical history; QOD, every other day; SADBE, squaric acid dibutylester; WBC, white blood cell count. Four of 6 patients demonstrated some regrowth of hair. Patient 1 had 20% regrowth of eyebrows. Patient 2 had 75% regrowth of upper eyelashes. Patients 3 and 4 had 95% and 80% regrowth of scalp hair, respectively. There were no serious adverse effects. Two patients using tofacitinib 2% cream demonstrated mild laboratory abnormalities, which could not definitively be attributed to treatment; their condition normalized after 3 months of ongoing treatment. Patient 4 had no response to topical tofacitinib 2% compounded in VersaBase cream (a nonliposomal base) but had complete hair regrowth with application of tofacitinib 2% in a liposomal base in areas of alopecia that had been persistent and stable for over 1 year (Fig 1, A and B). In these 6 pediatric patients, topical formulations of tofacitinib and ruxolitinib in 1%-2% concentrations were well-tolerated by all and beneficial for most. The experience of patient 4 suggests that a liposomal base, while less cosmetically elegant than VersaBase cream, might provide greater efficacy. Given that AA can resolve spontaneously, a definitive response to any treatment is difficult to assess. Additional studies will be important to elucidate patient factors that affect response to treatment, determine optimal formulation and dosing regimens, and delineate parameters for laboratory monitoring. Clinical trials exploring the use of topical JAK inhibitors for AA are presently underway (clinicaltrials.gov identifiers NCT02812342 and NCT02553330). Topical JAK inhibitors represent a promising therapeutic option for at least a subset of patients with AA. If confirmed to be effective in clinical trials, topical administration might be preferable for certain populations, including children and patients with more limited disease.